Common maternal infections during pregnancy and childhood leukaemia in the offspring: Findings from six international birth cohorts

Jian Rong He, Jane E. Hirst, Gabriella Tikellis, Gary S. Phillips, Rema Ramakrishnan, Ora Paltiel, Anne Louise Ponsonby, Mark Klebanoff, Jørn Olsen, Michael F.G. Murphy, Siri E. Håberg, Stanley Lemeshow, Sjurdur F Olsen, Xiu Qiu, Per Magnus, Jean Golding, Mary H. Ward, Joseph L. Wiemels, Kazem Rahimi, Martha S. LinetTerence Dwyer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data. Methods: Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-Associated symptoms (fever and diarrhoea) during pregnancy. Covariate-Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models. Results: Among 312a879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10-2.58)] and subtypes ALL [1.49 (0.87-2.56)] and AML [2.70 ([0.93-7.86)], but not with any cancer [1.13 (0.85-1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06-2.34)], ALL [1.43 (0.94-2.19)], AML [2.37 (1.10-5.12)] and any cancer [1.33 (1.09-1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes. Conclusions: Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.

Original languageAmerican English
Pages (from-to)769-777
Number of pages9
JournalInternational Journal of Epidemiology
Volume51
Issue number3
DOIs
StatePublished - 13 Jun 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Keywords

  • Maternal infection
  • childhood leukaemia
  • cohort study
  • prenatal

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